Summary:
A massive study of more than 187,000 older adults enrolled in the NIH’s All of Us Research Program reveals that adults with attention-deficit/hyperactivity disorder (ADHD) face more than quadruple the risk of developing dementia or mild cognitive impairment. Led by researchers at the University of Pittsburgh School of Medicine and published in JAMA Psychiatry, the study paired electronic health records with polygenic risk scores. Even without an official clinical diagnosis, individuals carrying elevated genetic risk for ADHD had a 35% higher chance of cognitive decline, demonstrating that the link is rooted in shared biology rather than diagnostic overlap.
Key Facts:
- Quadrupled Risk of Cognitive Impairment: Older adults with ADHD had more than four times the risk of progressing to dementia or mild cognitive impairment after adjusting for age, biological sex, and comorbid health conditions.
- Genetic Predisposition Confirmed: Independent of clinical diagnoses, participants possessing the highest polygenic risk scores for ADHD faced a 35% greater likelihood of developing dementia compared to those with the lowest genetic risk.
- Compounded Daily Burden: Patients navigating both ADHD and dementia reported worse overall mental health, lower life satisfaction, and required approximately 20% more healthcare resources in the year following their cognitive diagnosis.
Source: University of Pittsburgh
Attention-deficit/hyperactivity disorder (ADHD) has long been viewed through the lens of childhood and early adulthood—characterized by chronic inattention, executive dysfunction, impulsivity, and emotional dysregulation. However, growing epidemiological research indicates that ADHD persists across the entire adult lifespan, bringing cumulative neurobiological and behavioral consequences.
In recent years, smaller clinical registries in Scandinavia and Europe suggested that adults with ADHD might be unusually vulnerable to neurodegenerative diseases in late life. Yet clinicians remained divided over whether this association reflected true biological vulnerability or a diagnostic artifact: could early, subtle stages of Alzheimer’s disease and vascular dementia merely be misdiagnosed as late-emerging adult ADHD?
Now, an investigation led by the University of Pittsburgh School of Medicine provides the most comprehensive evidence to date that ADHD and cognitive decline share deep clinical and genetic foundations.
Published in JAMA Psychiatry, the study evaluated health records and genomic data from more than 187,000 diverse participants aged 50 and older enrolled in the National Institutes of Health’s All of Us Research Program. The team discovered that diagnosed adults face more than four times the risk of developing cognitive impairment, and that the underlying genetic risk variants for ADHD independently accelerate cognitive deterioration.
“This doesn’t prove that ADHD causes dementia, but seeing the same pattern show up independently in medical records and in people’s genes gives us greater confidence that the association is not simply an artifact of how ADHD gets diagnosed,” said senior author Tharick A. Pascoal, M.D., Ph.D., associate professor of psychiatry and neurology at the University of Pittsburgh School of Medicine. “Two different kinds of evidence are pointing in the same direction.”
Genomic Evidence From the All of Us Cohort
To determine whether the diagnostic link was genuine, the researchers examined longitudinal health records from 187,000 older adults. Overall, 6.7% of participants diagnosed with ADHD developed dementia or mild cognitive impairment, compared with 3.4% of those without the condition.
After controlling for potential confounders, including chronological age, biological sex, cardiovascular comorbidities, and socio-demographic indicators, the adjusted hazard ratio revealed that an ADHD diagnosis was associated with a greater than fourfold increase in the long-term risk of developing cognitive decline.
To address the concern of reverse causality, the possibility that early, prodromal dementia was simply being mislabeled as adult-onset ADHD, the team instituted an eight-year analytical buffer. Even when requiring that at least eight full years elapse between an ADHD diagnosis and the onset of cognitive symptoms, the elevated risk remained robust and statistically significant.
Crucially, the investigators integrated genomic profiling by calculating ADHD polygenic risk scores (PRS)—a quantitative metric aggregating common single-nucleotide polymorphisms associated with ADHD across the genome.
Participants in the highest tier of genetic vulnerability displayed a 35% higher incidence of dementia compared to those in the lowest risk tier, even among individuals who had never received a clinical diagnosis of ADHD during their lifetime.
“We’re replicating a pattern that’s been observed in other countries, now in a large U.S. sample, and adding genetic evidence on top of it,” said co-lead author Douglas Teixeira Leffa, M.D., Ph.D., who recently completed his psychiatry residency at UPMC. “That combination gives us more confidence that ADHD deserves a closer look as a potential factor in cognitive aging.”
The Compounded Clinical Burden of Dual Diagnoses
Beyond diagnosing risk, the researchers analyzed the lived experience of patients carrying both conditions.
Among participants who developed mild cognitive impairment or dementia, individuals with comorbid ADHD experienced significantly poorer functional outcomes than those managing dementia alone. They reported:
- Elevated rates of secondary depression and internalizing distress
- Lower subjective life satisfaction and reduced social engagement
- An approximate 20% surge in total healthcare utilization across the 12 months following their formal cognitive diagnosis
“Analyzing genetic information alongside years of health records allows us to identify patterns that might not be visible in a smaller or more traditional study,” noted co-first author Guilherme Bauer-Negrini, Ph.D., a postdoctoral associate in biomedical data science at Pitt. “With this kind of data, we can start to investigate what may be driving this association and whether any of those factors could be modified to support healthier cognitive aging.”
Therapeutic Questions and Future Directions
The findings expand upon earlier work from the Pascoal laboratory, which in 2022 first demonstrated that genetic liability for ADHD was linked to amyloid and tau pathology deposition in cognitively unimpaired older individuals.
The discovery highlights several pressing questions for neuropsychiatry:
- The Pharmacological Variable: Do long-term central nervous system stimulant medications (such as methylphenidate or amphetamine formulations) attenuate or exacerbate downstream dementia risk by supporting dopamine and norepinephrine tone?
- Cardiovascular & Lifestyle Mediators: Because adults with untreated ADHD frequently face higher rates of sleep disruption, chronic stress, smoking, and metabolic dysregulation, could aggressive mid-life cardiovascular and sleep management decouple ADHD from late-life dementia?
While the researchers emphasize that having ADHD does not make dementia inevitable, the presence of genetic and clinical convergence highlights adult ADHD as a modifiable risk factor requiring proactive, lifelong cognitive monitoring.
Funding: This research was supported by the National Institute on Aging (R01 AG073267, R01 AG075336), the Alzheimer’s Association (AARF-D-23-1150249, AARFD-22-923814, AARFD-22-974627, 24AARFD-1243899), the U.K. National Institute for Health and Care Research (NIHR303122, NIHR203684, NIHR203035, NIHR130077, NIHR128472, RP-PG-0618-20003), and the European Research Executive Agency (101095568 HORIZONHLTH- 2022-DISEASE-07-03).
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this Neurology and Neuropharmacology Research:
- Media Contact: Liz Reid
- Source: UPMC
- Image Credit: Image credited to Neuroscience News
- Original Research is Open Access: JAMA Psychiatry (Oct 7, 2026). “Attention-Deficit/Hyperactivity Disorder and Late-Life Cognitive Impairment.” Authors: Guilherme Bauer-Negrini, Douglas Teixeira Leffa, Pamela C. L. Ferreira, Bruna Bellaver, Guilherme Povala, Marina S. Medeiros, Firoza Z. Lussier, Dana L. Tudorascu, Samuele Cortese, Luis Augusto Rohde, Brooke S. G. Molina, and Tharick A. Pascoal.
- DOI: 10.1001/jamapsychiatry.2026.3165
Abstract
Attention-Deficit/Hyperactivity Disorder and Late-Life Cognitive Impairment
Importance
Attention-deficit/hyperactivity disorder (ADHD) affects tens to hundreds of millions of adults worldwide, and preliminary evidence suggests it may be associated with increased risk of mild cognitive impairment (MCI) and dementia. However, concerns regarding diagnostic ascertainment and residual confounding remain.
Objective
To investigate the association of ADHD with incident cognitive impairment, defined as MCI or dementia, using electronic health record (EHR) diagnoses and genetic liability measured using genome-wide ADHD polygenic risk score (ADHD PRS) in the same individuals.
Design, Setting, and Participants
This cohort study used data from the US All of Us Research Program (enrollment May 6, 2018, to October 1, 2023; EHR data from January 4, 1985, to October 1, 2023; mean [SD] follow-up 10.26 [6.75] years). A total of 187 341 participants aged 50 years and older with available EHR and genomic data were included. Data were analyzed from October 2025 to July 2026.
Exposures
ADHD diagnosis and ADHD PRS.
Main Outcomes and Measures
Incident MCI or dementia.
Results
Among 187 341 participants (mean [SD] age, 56.41 [7.88] years; 107 266 [57%] female), 3026 (1.6%) had ADHD. Among participants with ADHD, 203 (6.7%) developed cognitive impairment, compared with 6259 (3.4%) among those without ADHD. In adjusted Cox models, ADHD was associated with a more than 4-fold higher hazard of cognitive impairment (hazard ratio [HR], 4.60; 95% CI, 3.99-5.29; P < .001). Adjustments for comorbidities, educational attainment, and health care utilization attenuated but did not eliminate the association.
Similarly, ADHD PRS was associated with incident cognitive impairment (highest vs lowest quintile: HR, 1.35; 95% CI, 1.25-1.46; P < .001). Among participants who developed cognitive impairment, comorbid ADHD diagnosis was associated with a nearly 2-fold higher odds of suboptimal mental health (odds ratio [OR], 1.69; 95% CI, 1.18–2.39; P = .01), quality of life (OR, 1.66; 95% CI, 1.14-2.39; P = .02), social satisfaction (OR, 2.39; 95% CI, 1.69–3.37; P < .001), and 20% higher health care utilization (incidence rate ratio, 1.20; 95% CI, 1.09–1.34; P = .003), suggesting greater care burden beyond the elevated incidence risk.
Conclusions and Relevance
In this cohort study, convergent clinical and genetic evidence revealed ADHD was associated with a markedly increased risk of late-life cognitive impairment. Among those who develop cognitive impairment, an ADHD diagnosis was associated with worse health outcomes and greater health care utilization, supporting the need for targeted monitoring and integrated care in this population.
